液相色谱-串联质谱法测定人血浆中的头孢替安浓度

为评价盐酸头孢替安酯片在健康人体内的药代动力学特征,应用蛋白沉淀-液相色谱-串联质谱技术建立了灵敏度高、特异性强、快速的健康受试者血浆中头孢替安的分析方法。选用 Waters Symmtry C18色谱柱(50 mm×4.6 mm,5μm),以甲醇和1 mmol/ L 乙酸铵水溶液梯度洗脱,流速1.0 mL/ min。在多反应监测模式(MRM)下,采用电喷雾离子化源,正离子扫描模式下进行定量分析。标准曲线在5.0~5000 ng/ mL 范围内线性关系良好(r>0.99),定量下限为5.0 ng/ mL,方法学验证部分结果均符合生物样本定量测定的要求。本方法快速、灵敏、重现性好,并成功应用于健康受试者盐酸头孢替安酯片药动学研究,同时也为同类药物在人体生物基质中的定量检测提供参考。

Determination of Cefotiam in Human Plasma Using Liquid Chromatography-Tandem Mass Spectrometry

In order to evaluate the pharmacokinetic profile of cefotiam hexetil hydrochloride tablet in Chinese healthy volunteers, a sensitive, specific and rapid " protein precipitation-liquid chromatography-tandem mass spectrometry" method was developed and validated in human plasma. Chromatographic separation was achieved on a Waters Symmtry-C18 column (50 mm × 4. 6 mm, 5 μm), using a gradient mobile phase consisting of methanol and 1 mmol/ L ammonium acetate in water at a flow rate of 1. 0 mL/ min. Cefotiam and diazepam (internal standard) were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The calibration curve was linear from 5. 0 ng / mL to 5000 ng / mL (r>0. 99) with limit of quantitation of 5. 0 ng / mL. The assay met the published acceptance criteria. This rapid, sensitive and reproducible method was successfully applied to the pharmacokinetic study of cefotiam hexetil hydrochloride tablet in healthy Chinese volunteers and therefore provided a considerable mirror for quantification of other cephalosporins in human matrix.